G-proteins (GTP binding regulatory proteins) are the fundamental mediators of a variety of membrane receptors. These proteins can be extracted from cell membranes with the detergent octylglucoside (OG) to yield large, polydisperse structures that have hydrodynamic characteristics similar to such polymeric structures as actin and tubulin. These structures are destroyed by most other detergents, including cholate which reduces G-proteins to heterotrimeric proteins. The polymer-like structures of G-proteins disaggregate into much smaller (monomers) when subjected to guanine nucleotides or fluoride ion. When intact liver membranes are treated with glucagon and GTP-gamma-S and extracted with OG, only the largest of the polymer-like structures are converted to monomers suggesting that the glucagon receptor preferentially interacts with "multimers" of G-proteins. Also established is that G-proteins are taken up by both adipocytes and CHO cells into endocytic vesicles; the endocytic process is regulated by B-adrenergic (adipocytes) and muscarinic receptors (CHO cells containing transfected muscarinic receptors). These findings raise the possibility that signal transduction takes place both at the surface membrane and during the trafficking of endosomes containing the signalling elements.